HTLV-1 targets human placental trophoblasts in seropositive pregnant women

J Clin Invest. 2020 Nov 2;130(11):6171-6186. doi: 10.1172/JCI135525.

Abstract

Human T cell leukemia virus type 1 (HTLV-1) is mainly transmitted vertically through breast milk. The rate of mother-to-child transmission (MTCT) through formula feeding, although significantly lower than through breastfeeding, is approximately 2.4%-3.6%, suggesting the possibility of alternative transmission routes. MTCT of HTLV-1 might occur through the uterus, birth canal, or placental tissues; the latter is known as transplacental transmission. Here, we found that HTLV-1 proviral DNA was present in the placental villous tissues of the fetuses of nearly half of pregnant carriers and in a small number of cord blood samples. An RNA ISH assay showed that HTLV-1-expressing cells were present in nearly all subjects with HTLV-1-positive placental villous tissues, and their frequency was significantly higher in subjects with HTLV-1-positive cord blood samples. Furthermore, placental villous trophoblasts expressed HTLV-1 receptors and showed increased susceptibility to HTLV-1 infection. In addition, HTLV-1-infected trophoblasts expressed high levels of viral antigens and promoted the de novo infection of target T cells in a humanized mouse model. In summary, during pregnancy of HTLV-1 carriers, HTLV-1 was highly expressed in placental villous tissues, and villous trophoblasts showed high HTLV-1 sensitivity, suggesting that MTCT of HTLV-1 occurs through the placenta.

Keywords: Epidemiology; Infectious disease; Virology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Female
  • HTLV-I Infections / metabolism*
  • HTLV-I Infections / pathology
  • HTLV-I Infections / transmission
  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • Infectious Disease Transmission, Vertical*
  • Pregnancy
  • Pregnancy Complications, Infectious / metabolism*
  • Pregnancy Complications, Infectious / pathology
  • Pregnancy Complications, Infectious / virology
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology
  • Trophoblasts / virology

Grants and funding

Grant-in-Aid for Scientific Research (C)